With increased awareness for the detrimental impact of metals on human health and environment, it is highly desirable to develop more sensitive and selective probes for the detection of metal ions in biological and environmental samples. A variety of divalent metal ions are known to be involved in the structural, catalytic, and regulatory aspects of the biological system, and some such metal ions serve as prognostics of certain human diseases. For example, Cu2+, Zn2+, and Fe2+ have been found to be involved in aggregating β-amyloid peptides during the onset of the Alzheimer's disease. However, due to the lack of metal ion specific probes, the relative contribution of one type of metal ion versus the other in causing the disease is not clearly understood. The inability to differentiate among different types of divalent metal ions in biological samples has been one of the major impediments in the area of bio-analytical chemistry.
Although there has been some success in detection of biologically significant metal ions by developing fluorescence probes (e.g., fura-2 for Ca2+), most of the probes exhibit cross reactivity for other metal ions. This is not surprising since both physical and electronic properties of these metal ions are not too disparate, and they tend to exhibit comparable binding affinities with their cognate chelating agents. Consequently, not only synthetic (organic) probes but also enzymatic probes exhibit cross-reactivities among metal ions. Presently, quinoline-sulfonamide containing compounds and their derivatives are regarded to be as the “gold” standards for detecting low concentrations of Zn2+, albeit such compounds also exhibit selectivity for Cu2+. The origin of such selectivity appears to be encoded by facile changes in the coordination state of Zn2+ versus Cu2+. Unexpectedly, the invention herein describes a method for the synthesis and use of novel Zn2+ selective fluorescent compounds that exhibit a high specificity for Zn2+ with low reactivity to other divalent metal ions.